t(17;21)(q11.2;q22) as a sole aberration in acute myelomonocytic leukemia

Case report of a translocation : t(17;21)(q11.2;q22) as a sole aberration in acute myelomonocytic leukemia

Complex systems and the technology of variability analysis

Characteristic patterns of variation over time, namely rhythms, represent a defining feature of complex systems, one that is synonymous with life. Despite the intrinsic dynamic, interdependent and nonlinear relationships of their parts, complex biological systems exhibit robust systemic stability. Applied to critical care, it is the systemic properties of the host response to a physiological insult that manifest as health or illness and determine outcome in our patients. Variability analysis provides a novel technology with which to evaluate the overall properties of a complex system. This review highlights the means by which we scientifically measure variation, including analyses of overall variation (time domain analysis, frequency distribution, spectral power), frequency contribution (spectral analysis), scale invariant (fractal) behaviour (detrended fluctuation and power law analysis) and regularity (approximate and multiscale entropy). Each technique is presented with a definition, interpretation, clinical application, advantages, limitations and summary of its calculation. The ubiquitous association between altered variability and illness is highlighted, followed by an analysis of how variability analysis may significantly improve prognostication of severity of illness and guide therapeutic intervention in critically ill patients

Identification of an excellent prognosis subset of human papillomavirus-associated oropharyngeal cancer patients by quantification of intratumoral CD103+ immune cell abundance

BACKGROUND: Accurate prognostic stratification of human papillomavirus-associated oropharyngeal cancers (HPV+OPSCC) is required to identify patients potentially suitable for treatment deintensification. We evaluated the prognostic significance of CD103, a surface marker associated with tissue-resident memory T cells (TRMs), in two independent cohorts of patients with HPV+OPSCC. PATIENTS AND METHODS: The abundance and distribution of CD103+ immune cells were quantified using immunohistochemistry in a cohort of 189 HPV+OPSCC patients treated with curative intent and correlated with outcome. Findings were then validated in an independent cohort comprising 177 HPV+OPSCCs using univariable and multivariable analysis. Intratumoral CD103+ immune cells were characterized by multispectral fluorescence immunohistochemistry and gene expression analysis. RESULTS: High intratumoral abundance of CD103+ immune cells using a  ≥30% cut-off was found in 19.8% of tumors in the training cohort of HPV+OPSCC patients and associated with excellent prognosis for overall survival (OS) with adjusted hazard ratio (HR) of 0.13 [95% confidence interval (CI) 0.02-0.94, P = 0.004]. In the independent cohort of HPV+OPSCCs, 20.4% had high intratumoral CD103+ abundance and an adjusted HR for OS of 0.16 (95% CI 0.02-1.22, P = 0.02). Five year OS of patients with high intratumoral CD103 was 100% across both cohorts. The C-statistic for the multivariate prognostic model with stage and age was significantly improved in both cohorts with the addition of intratumoral CD103+ cell abundance. On the basis of spatial location, co-expression of CD8 and CD69, and gene expression profiles, intratumoral CD103+ cells were consistent with TRMs. CONCLUSION: Quantification of intratumoral CD103+ immune cell abundance provides prognostic information beyond that provided by clinical parameters such as TNM-staging, identifying a population of low risk HPV+OPSCC patients who are good candidates for trials of deintensification strategies

Respiratory muscle activity related to flow and lung volume in preterm infants compared with term infants

Infants with chronic lung disease (CLD) have a capacity to maintain functional lung volume despite alterations to their lung mechanics. We hypothesize that they achieve this by altering breathing patterns and dynamic elevation of lung volume, leading to differences in the relationship between respiratory muscle activity, flow and lung volume. Lung function and transcutaneous electromyography of the respiratory muscles (rEMG) were measured in 20 infants with CLD and in 39 healthy age-matched controls during quiet sleep. We compared coefficient of variations (CVs) of rEMG and the temporal relationship of rEMG variables, to flow and lung volume [functional residual capacity (FRC)] between these groups. The time between the start of inspiratory muscle activity and the resulting flow (tria)--in relation to respiratory cycle time--was significantly longer in infants with CLD. Although FRC had similar associations with tria and postinspiratory activity (corrected for respiratory cycle time), the CV of the diaphragmatic rEMG was lower in CLD infants (22.6 versus 31.0%, p = 0.030). The temporal relationship of rEMG to flow and FRC and the loss of adaptive variability provide additional information on coping mechanisms in infants with CLD. This technique could be used for noninvasive bedside monitoring of CLD